Adrenergic Antagonists: ɑ and β-Receptor Blockers

Recall that conventional β-blockers primarily induce peripheral vasoconstriction. In contrast, third-generation β-blockers, such as labetalol and carvedilol, are additional α₁-adrenoceptor blockers, causing vasodilation.

This vasodilation occurs via various mechanisms, including increased nitric oxide production, calcium ion entry blockade, potassium ion channel opening, and antioxidant action.

Labetalol—comprising four isomers with distinct action on adrenoceptor subtypes—is commercially available as a racemic mixture.

It inhibits β₁, β₂ and α₁ receptors. β₁-blockade lowers blood pressure, while α₁-blockade reduces vascular resistance without impacting heart rate or cardiac output.

So, labetalol is clinically indicated in pheochromocytoma and hypertensive emergencies. Additionally, its low lipophilicity implies negligible placental transfer, making it safe for gestational hypertension.

Carvedilol, on the other hand, exhibits anti-inflammatory action and decreases lipid peroxidation and vascular wall thickening. It improves ventricular function in mild to extreme congestive heart failure and myocardial infarction.